Clinical Trials Register

Summary
EudraCT Number:	2014-000659-10
Sponsor's Protocol Code Number:	LMW-DS-103
National Competent Authority:	Sweden - MPA
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2014-03-27
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Sweden - MPA

A.2

EudraCT number

2014-000659-10

A.3

Full title of the trial

A randomised, open-label, placebo-controlled, single centre study in healthy male volunteers to explore efficacy, safety and tolerability of single doses of low molecular weight dextran sulfate (LMW-DS) in combination with recombinant human granulocyte colony stimulating factor (rhG-CSF, filgrastim) and in comparison with plerixafor treatment and placebo

En randomiserad, öppen, placebokontrollerad singelcenter studie utförd på friska manliga forskningspersoner med syfte att utvärdera effekt, säkerhet och tolerabilitet av engångsadministrering lågmolekylärt dextransulfat (LMW-DS) i kombination med rekombinant human granulocyt kolonistimulerande faktor (rhG-CSF) jämfört med plerixafor behandling och placebo

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A.4.1

Sponsor's protocol code number

LMW-DS-103

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	TikoMed AB
B.1.3.4	Country	Sweden
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Apotek Produktion & Laboratorier AB
B.4.2	Country	Sweden
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	PCG Clinical Services AB
B.5.2	Functional name of contact point	Linn Skärberg
B.5.3	Address:
B.5.3.1	Street Address	Kungsängsvägen 19
B.5.3.2	Town/ city	Uppsala
B.5.3.3	Post code	753 23
B.5.3.4	Country	Sweden
B.5.4	Telephone number	+46708 46 83 40
B.5.5	Fax number	+4618431 30 01
B.5.6	E-mail	linn.skarberg@pharmaconsultinggroup.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EMA/COMP/335174/2011
D.3 Description of the IMP
D.3.1	Product name	LMW-DS solution
D.3.4	Pharmaceutical form	Solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	-
D.3.9.1	CAS number	9011-18-1
D.3.9.2	Current sponsor code	DSSS5
D.3.9.3	Other descriptive name	DEXTRAN SULFATE SODIUM
D.3.9.4	EV Substance Code	SUB13554MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	20
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Neupogen Novum
D.2.1.1.2	Name of the Marketing Authorisation holder	Amgen Europe B.V.
D.2.1.2	Country which granted the Marketing Authorisation	Sweden
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Neupogen Novum
D.3.4	Pharmaceutical form	Solution for injection in pre-filled syringe
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	FILGRASTIM
D.3.9.1	CAS number	121181-53-1
D.3.9.4	EV Substance Code	SUB07627MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	0.6 to 0.96
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 3
D.1.2 and D.1.3	IMP Role	Comparator
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Mozobil
D.2.1.1.2	Name of the Marketing Authorisation holder	Genzyme Europe B.V.
D.2.1.2	Country which granted the Marketing Authorisation	Sweden
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EU/3/04/227
D.3 Description of the IMP
D.3.1	Product name	Mozobil
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	PLERIXAFOR
D.3.9.1	CAS number	110078-46-1
D.3.9.3	Other descriptive name	PLERIXAFOR
D.3.9.4	EV Substance Code	SUB28849
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	20
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for infusion
D.8.4	Route of administration of the placebo	Intravenous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Healthy volunteers (mobilization of haematopoietic stem cells)

Friska forskningspersoner (mobilisering av hematopoetiska stamceller)

E.1.1.1

Medical condition in easily understood language

Healthy subjects (release of stem cells)

Friska forskningspersoner (frisättning av stamceller)

E.1.1.2

Therapeutic area

Diseases [C] - Blood and lymphatic diseases [C15]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	17.0
E.1.2	Level	LLT
E.1.2	Classification code	10053948
E.1.2	Term	Hematopoietic stem cell mobilization
E.1.2	System Organ Class	100000004865

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

To determine the blood levels of CD34+ cells at different time points after treatment with filgrastim (for 5 days) in combination with low molecular weight dextran sulfate (LMW-DS) compared to filgrastim treatment (for 5 days) in combination with plerixafor or NaCl.

Att utvärdera antal CD34+ celler under olika tidpunkter efter behandling med filgrastim (under 5 dagar) i kombination med lågmolekylärt dextransulfat (LMW-DS) jämfört med filgrastim behandling (under 5 dagar) i kombination med plerixafor eller natriumklorid.

E.2.2

Secondary objectives of the trial

• to evaluate safety and tolerability
• to measure WBCs and lymphocytes
• to measure the levels of HGF
• to measure the levels of SDF-1
• to measure the effect on APTT

• att utvärdera säkerhet och tolerabilitet
• att utvärdera vital blodkroppar och lymfocyter
• att utvärdera HGF-nivåer
• att utvärdera SDF-1-nivåer
• att utvärdera effekt på APTT

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1) Male subjects, 18 to 50 years of age, at the time of informed consent
2) Body Weight ≥60 to ≤95 kg
3) Signed Informed Consent
4) Healthy according to medical history including bleeding tendency for the participant or first degree family members. Laboratory analyses for PK(INR), fibrinogen, Von Willebrand´s factor and APTT must be within normal range at screening.

1) Manliga forskningspersoner, 18 till 50 år (vid tidpunkt för signering av informerat samtycke)
2) Kroppsvikt ≥60 till ≤95 kg
3) Signerat samtycke
4) Friska, enligt anamnes, inklusive blödningsbenägenhet för forskningspersonen eller förekommande hos närmaste familj. Labtester för PK(INR), fibrinogen, Von Willenbrands faktor och APTT måste vara inom normalt referensintervall på screeningbesöket.

E.4

Principal exclusion criteria

1) Any medication including herbal remedies and over the counter (OTC) drugs (except for paracetamol) within 14 days prior to study drug administration
2) Positive urine drug screen and alcohol breath test
3) Positive test result for hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV), human immunodeficiency virus (HIV) antibody/antigen, at Screening.
4) Intake of any other study medication within 90 days prior to screening
5) Blood or plasma donation/loss of more than 400 mL within 90 days prior to study drug administration
6) Clinically significant deviations from normal values for vital signs, ECG and laboratory tests.
7) Current nicotine user
8) Evidence of clinically significant orthostatic symptoms (eg, dizziness upon standing) or systolic BP drop ≥20 mm Hg or diastolic BP drop ≥10 mm Hg from supine to standing assessment at screening. An increase in pulse of >30 beats per minute (bpm) or an increase in pulse >120 bpm from supine to standing at screening.
9) Allergy at the discretion of the investigator
10) Any condition that, in the Investigator’s opinion, may interfere with a subject’s ability to comply with the study protocol
11) Any other condition which, in the Investigator’s opinion, would make the
subject unsuitable for inclusion into the trial

1) Annan medicinering inklusive naturläkemedel och receptfria läkemedel (förutom paracetamol) inom 14 dagar före administrerng av studieläkemedel
2) Positiv drogtest (urin) och alkotest (utandningstest)
3) Positiva testresultat för hepatit B och C, human immunodeficiency virus (HIV) vid screening.
4) Intag av annat studieläkemedel inom 90 dagar före screening
5) Blod- och/eller plasma donation/förlust av mer än 400 mL inom 90 dagar före administrering av studieläkemedel.
6) Kliniskt relevanta avvikelser från normalt intervall och påverkan på hemostatisk anamnes
7) Nikotinanvändning (pågående)
8) Bevis på kliniskt signifikanta ortostatiska symptom (t ex. yrsel när man reser sig) eller systoliskt blodtrycksfall ≥20 mm Hg eller diastoliskt blodtrycksfall ≥10 mm Hg från liggande till stående utvärdering under screening. En pulsökning med >30 slag/min eller en ökad puls >120 slag/min från liggande till stående under screening.
9) Allergi - efter prövarens bedömning
10)Tillstånd som, enligt prövarens bedömning, kan påverka forskningspersonens förmåga att följa studieprotokollet
11) Tillstånd som, enligt prövarens bedömning,
bedöms att kunna påverka forskningspersonen som icke lämplig till deltagande i studien.

E.5 End points

E.5.1

Primary end point(s)

Absolute number, fold increase, peak fold change compared to pre-dose values and area under the curve (AUC) of circulating CD34+ cells for all treatment groups will be assessed on Day 5 (cells are counted over 24 hours after LMW-DS/plerixafor/NaCl treatment)

Absolut antal, ökning, maximal ökning, jämfört med före dosering och area under kurvan (AUC) av cirkulerande CD34+ celler för alla behandlingsgrupper kommer att utvärderas på Dag 5 (under24 timmar efter LMW-DS/plerixafor/NaCl behandling)

E.5.1.1

Timepoint(s) of evaluation of this end point

CD34+ will be assessed 30 minutes before start of LMW-DS infusion/plerixafor injection/NaCl infusion (Day 5) and at 1, 3, 6, 9 and 24 h post start of LMW-DS infusion/plerixafor injektion/NaCl infusion.

CD34+ kommer att mätas 30 minuter efter påbörjad LMW-DS infusion/plerixafor injektion/NaCl infusion (Day 5) och vid 1, 3, 6, 9 och 24 h efter påbörjad LMW-DS infusion/plerixafor injektion/NaCl infusion.

E.5.2

Secondary end point(s)

None

Inga

E.5.2.1

Timepoint(s) of evaluation of this end point

N/A

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

Yes

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

Yes

E.7.1.3.1

Other trial type description

Phase I/IIa efficacy, safety and tolerability study

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

Last visit last subject

Sista besök sista subjekt

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

Yes

F.3.2

Patients

F.3.3

Specific vulnerable populations

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

None

Inga.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2014-05-21

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2014-04-23

P. End of Trial
P.	End of Trial Status	Prematurely Ended

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IMP with orphan designation in the indication
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